Very few quantitative observations have been reported on the effect of rate of breathing on the voluntary maximum breathing capacity (M.B.C.). Proctor and Hardy (1949) found that the M.B.C. was achieved at a rate of 30 respirations per minute (R.P.M.). At higher rates of breathing the ventilatory capacity was diminished. These observations are contrary to the findings of other investigators who regard a fast rate of breathing as essential in producing the largest value for the M.B.C. (Gray and Green, 1945;Baldwin, Cournand, and Richards, 1948). None of these investigators used spirometers which had been tested for recording errors (Bernstein and Mendel, 1951), nor were the observations made at controlled rates of breathing.The effect of rate of breathing on the M.B.C.of a group of normal subjects has been investigated. This work has been performed on a spirometer which is substantially free from recording error. It has been suggested that to control the rate of breathing impairs the subject's performance, but evidence is provided here to show that there is no sound basis for that opinion. THE DESIGN OF THE SPIROMETERRecently Bernstein and Mendel (1951) showed that a spirometer of the conventional pattern commonly used for the M.B.C. test could give records of breathing which were grossly inaccurate. The respiratory rates at which these inaccuracies occurred were determined by the mean depth of immersion of the spirometer bell in its water-jacket, while their extent was determined by the rate, volume, and wave-form of the respiratory air-flow. Because these factors are variable in human experiments, an appropriate correction factor, applicable to every estimation on any one apparatus, cannot be deduced. It was also shown that these inaccuracies were due, at least in part, to the inertia of the moving parts of the spirometer. This caused pressure changes to occur within the bell, and these, at certain respiratory rates, tended to excite i esonance in the water column in the water-jacket. The respiratory rate at which resonance occurred was dependent on the length of the water column.By altering the design it has been possible to build a spirometer which is substantially free from recording error up to a rate of 110 R.P.M. This range is considerably greater than is possible with our conventional (Knipping) spirometer, with which aspiration of water into the connecting tubes commonly occurs at respiratory rates above about 55 R.P.M.The design considerations were as follows:To REDUCE THE INERTIA OF THE MOVING PARTS.-This has been achieved as follows:Reducing the Mass of the Bell.-In order to do this the bell was made of aluminium sheet, which is very light and strong, and its proportions were altered so as to give a better ratio between contained volume and surface area. The ideal bell would have equal length and cross-sectional diameter. This ideal has been approached, though not attained, because a compromise was adopted in which the cross-sectional area was made twice as great as that of the bell of the Knipping s...

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If a limb of an anaesthetized animal is intermittently tetanized for a few minutes, the muscles soon become swollen, turgid and pink, and the water content increases considerably. Such effects might be produced by swelling of the fibres or by extracellular and circulatory changes. In this study it is shown that the increased inulin space partly accounts for the rise in water content on stimulation. In addition, measurement of fibre diameter showed no significant increase after tetanization. These results have also been used to calculate internal ion concentrations. METHODSInulin 8pace. Mature rats were anaesthetized with ether, nephrectomized, and 2 ml. of a warm supersaturated solution of inulin (25 %, w/v) which had previously been filtered, was injected into the external jugular vein. The rats were allowed to recover. After 2-5 hr, sodium amylobarbitone was injected into the peritoneal cavity, 0.1 ml. of a 10% (w/v) solution per 100 g being used. In some cases, the sciatic nerve was then stimulated. Blood and gastrocnemius muscle were later removed. Visible fat was cut away from the muscle, and the latter was usuallydividedintotwo, half being retained for estimation of water and cations, while the other half was required for estimation of inulin in muscle and plasma using the procedure of Ross & Mokotoff (1951). Blank values, obtained by dummy experiments without inulin, were subtracted in each case. It was found that a larger dose of barbiturate diminished the response of the muscle to stimulation and there was then no increase in the inulin space.Blood content. Blood in muscle was estimated as alkaline haematin, as used by Conway & Fearon (1944), the colorimetric procedure being that described by Boyle, Conway, Kane & O'Reilly (1941). The blank value, which was equivalent to 1F7 g/100 g, was obtained from the gastrocnemius muscle after perfusion with Krebs solution (saline) for 3 hr, which may have removed some myoglobin.Stimulation. The sciatic nerve of a rat, anaesthetized as above, was exposed and stimulated during each alternate second; a succession of single maximal shocks at a rate of 10/sec was employed to produce intermittent incomplete tetani. A constant-current stimulator with a rectangular-shaped output was used (Bernstein, 1950), with duration 0-5 msec. A load of 5% body weight was attached to the leg, and the latter operated a lever whose excursions were recorded on a slow drum. Intermittent tetanization was continued for 30 min. This method of

IN a previous communication it was shown [D'Silva, 1936b] that the liberation of potassium by adrenaline in the perfused cat's liver was facilitated by the presence of oxygen. Larger quantities of the base were set free when the perfusion was carried out with blood than when van Dyke & Hastings' fluid was used. Evidence was adduced to show that asphyxia of the tissues attendant on the use of the inorganic fluid was not responsible for the results. Further, before the organ was capable of responding to a second dose of the drug, a period of recovery (oxidative) was necessary. In the present investigation various factors which might be concerned in the liberation of potassium have been studied further. METHODSCats anaesthetized with chloralose after ether were used. In all cases the animals were allowed to rest after the induction of anesthesia, for large amounts of ether have a tendency to increase the serum potassium [D'Silva, 1934]. Potassium was estimated by the method of Kramer & Tisdall [1921] as modified by Hubbard [1933]. Some of the experiments were carried out on the perfused liver. The technique of establishing perfusion and of collecting and analysing the effluent fluid has been described previously [D'Silva, 1936a]. RESULTS Response of the intact animal to successive doses of adrenalineThe injection of 0 05 mg. of adrenaline into an arm vein resulted in a large increase in the concentration of potassium in the serum [D'Silva, 1934]. Comparable increases in serum potassium were obtained when

The environment of cells in animal tissues is believed to consist of the interstitial fluid, and though this has been much considered in physiological writings it has usually been studied only by indirect means. There have been few attempts to collect and analyse this fluid by direct methods. Maurer (1938) in W. 0. Fenn's laboratory passed capillary tubes into the muscles of frogs and obtained small quantities of fluid which contained a high protein content. Manery (1954) doubted whether this was interstitial fluid and suggested that the amount of fluid between the fibres was so low that collection was impracticable. She considered that the fluid collected by Maurer might have been oedema fluid induced by tissue damage during the passage of the capillary tubes into the muscles, and this objection remained unanswered.The question has been studied anew by the intravenous injection of labelled proteins at various times before collection of the interfibre fluid, and the results give some support for the view that it is interstitial fluid which has been collected in the present case. These studies have been made on mammalian muscle and the opportunity has also been taken to make an analysis of the proteins of the fluid. METHODSPreparation of capillary tube8. Capillary tubes were drawn by hand from clean heavywalled soda-glass tubing of 7-8 mm outside diameter, one end of each capillary tube being flamed to round off rough edges. Capillary tubes were boiled in distilled water, washed repeatedly in acetone and dried in an oven. The range of external diameters of the tubes, measured with a micrometer, was 0-27-0-50 mm.Collection of samples of fluid. Male guinea-pigs of 260-600 g wt. were anaesthetized with sodium pentobarbitone (Nembutal, Abbott Laboratories), the dose being 36 mg/kg given intraperitoneally. They were placed on a table whose temperature was maintained by a thermostat, and ether was given to deepen anaesthesia. The skin over the front of the thigh was reflected and any fat covering the quadriceps femoris muscle was removed. The surface of the muscle was wiped lightly with gauze to remove tissue fluid, and capillary tubes,